(5α,17β)-N-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-azaandrost-1-ene-17-carboxamide is generically known as Dutasteride.
Dutasteride is a synthetic 4-azasteroid compound, which is a selective inhibitor of the type 1 and type 2 isoforms of steroid 5α-reductase (5AR), with which it forms a stable enzyme complex, which inhibits the conversion of testosterone to 5α-dihydrotestosterone (DHT).
Dutasteride is marketed under the name Avodart® in the US. It has been approved for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men.
U.S. Pat. No. 5,565,467 disclosed Dutasteride and process for preparation. According to U.S. Pat. No. '467, Dutasteride may be prepared by reacting 3-oxo-4-androstene-17β-carboxylic acid (II) with thionyl chloride in presence of pyridine to produce 3-oxo-4-androstene-17β-carboxylic acid chloride (IIa), which is further reacted with 2,5-bis(trifluoromethyl)aniline (III) to produce 17β-N-[2,5-bis(trifluoromethyl)-phenyl]carbomoyl-1-androst-4-en-3-one (IV). Oxidation of 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbomoyl-1-androst-4-en-3-one (IV) by treating with aqueous sodium permanganate and sodium periodate under basic conditions produce 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbamoyl-5-oxo-A-nor-3,5-secoandrostan-3-oic acid (V), which is further treated with ammonia in ethylene glycol, followed by hydrogenation to produce 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbamoyl-4-aza-5α-androstan-3-one (VI). Dehydrogenating a compound (VI) using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and bis(trimethylsilyl)trifluoroacetamide in dry dioxane to produce Dutasteride (I).
The process is as shown in Scheme-I below:

U.S. Pat. No. '467 also discloses a variant process for the preparation of Dutasteride (I) by reacting 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid (VII) with thionyl chloride in presence of pyridine to produce 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid chloride (VIII), which is further reacted with 2,5-bis(trifluoromethyl)aniline (III) to produce Dutasteride (I).
The process is as shown in Scheme-II below:

The major disadvantage with the above process is the low yield (44%) and purity of Dutasteride (80% by HPLC) and not suitable for the preparation of Dutasteride (I) on commercial scale.
US 2005/0059692 A1 discloses a process for the preparation of Dutasteride (I), wherein 4-aza-5α-androst-1-en-3-one-17β-carboxamide (IX) is condensed with 2-iodo-1,4-bis(trifluoromethyl)benzene (X).
The process is as shown in Scheme-III below:

US 2007/0173523 A1 generically disclose a process for the preparation of Dutasteride (I), which comprises, reacting 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid (VII) with the compound of Formula (XI) to produce an intermediate compound of Formula (XII), which is further reacted with an amine of Formula (IIIa) to produce Dutasteride (I).
The process is as shown in Scheme-IV below:

The greater stability of the intermediate XII results in slow reaction with amine IIIa, making the process difficult on commercial scale.
Hence, there is a need to develop a process, which provides Dutasteride (I) with high yields and purity on commercial scale.
The present invention is specifically directed towards a process, wherein 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid (VII) is reacted with trifluoromethane sulfonic acid anhydride, before condensing with 2,5-bis(trifluoromethyl)aniline (III) to produce Dutasteride (I) of high purity and yield.